System Biology Study Group
Walker Research Group
Spring 2007
Definition: System Biology
The process of network of genomescale network reconstruction, followed
by the synthesis if in silico models
describing their functionalities, is the
essence of system biology.
Key concepts
• Enumeration of biological components; and
• Identification of the links that connect
processes
What is a system?
“...parts in interaction.”
Von Bertalanffy
General System Theory
1968
What is a system?
“A system is an assemblage or
combination of elements or parts
forming a complex or unitary whole,
such as a river system or a
transportation system…”
Blanchard and Farbrycky
System Engineering and Analysis
1998
Classification of Genetic Circuits
Biological Databases
.
.
.
.
Gene
Transfer
Gene sequences
Genes
Gene function
Gene family
Evolutionary
dynamics
Genetic Circuit
Energy
Metabolism
Information
Transport
Transcription
Metabolic Engineering
Cell fate
processes
Posttranslation Cell division
Cell motion
modifications Cell differentiation
Translation
Tissue Engineering
Source: Palsoson, B. 2006. System Biology
Some characteristics of genetic
circuits
Characteristics
Analysis Method
• They are complex
• Bioinformatics
• They are autonomous
• Control theory
• They are robust
• System science
• They function to execute
• Transport and kinetic
a physicochemical
process
• They have “creative
functions”
• They are conserved, but
can be adjusted
theory
• Bifurcation analysis
• Evolutionary dynamics
Source: Palsoson, B. 2006. System Biology
Four Principal Steps
1.Component
Plurality of –
omics
Gen-
2.Reconstruction
“systematic
annotation”
one set of
reactions
arising from
the genome
3.In silico
modeling
plurality of
methods
4.Hypothesis
generation and
testing.
Proteo-
Transcript-
Metabol-
Reconstruction of biochemical reaction network
Topology
Constraints
Dynamics
Senstivity
Noise
Phenotypic space “practically infinite” for most organisms
Source: Palsoson, B. 2006. System Biology
Systematic Annotation
Source: Palsoson, B. 2006. System Biology
Input-output Modeling of Poultry
Waste Management System
System of Linear Equations
Y1,3  Y0,3k1,3  0
(24)
Y2,3  Y0,3k2,3  0
(25)
Y1,4  Y0,4 k1,4  0
(26)
Y2,4  Y0,4 k2,4  0
(27)
Y1,6  Y0,6 k1,6  0
(28)
Y2,6  Y0,6 k2,6  0
(29)
Continuity Constraints:
n1 : Y2,1  Y0,2  0
(14)
n2 : Y0,2  Y0,3  0
(15)
n3 : Y1,3  Y0,4  Y2,6  0
(16)
n4 : Y1,4  Y0,5  0
(17)
n5 : Y1,7  Y2,4  Y2,3  0
(18)
n6 : Y0,6  Y1,1  0
(19)
System of Linear Equations for
Poultry Waste Problem
1 / k2,1

0
0

0
0

0

0
0

1

0
0

0
0

0
0
0
0
0
0
0
0
0
0
0
0
0
1 / k1,1 0
0
0
0
0
0
0
0
0
0
0
0
0
 k1,3
1
0
0
0
0
0
0
0
0
0
0
 k2 ,3
0
1
0
0
0
0
0
0
0
0
0
0
0
0  k1, 4 1
0
0
0
0
0
0
0
0
0
0  k2, 4 0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0  k1,6 1
0
0
0
0
0
0
0
0
0
0  k2, 6 0
0
0
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0 1
0 0
1 0
0
1
0
0 0
0 1
1 0
0
0
1
0
0
0
0
0
0
1
0
0
0
0
0
0
1
0
0
0
0
0  Y2,1  Y 
 Y1,1   0,1 
0   Y
 0,1 


Y

0  0 , 2  0 

 
0  Y0,3  0 
 
0  Y1,3  0 
 
0  Y2,3  0 
 Y   
0   0, 4   0
Y  0 

1  1, 4   

 
0  Y2, 4  0 
 Y  0 
0   0,5 
 
 1 Y1,7  0 
   0 
0 Y0,6 
0 



0 Y1,6
 
   0 
0  Y2,6   
(35)
Roots of System Biology
Source: Palsoson, B. 2006. System Biology
Component View
Source: Palsoson, B. 2006. System Biology
Links
Links between molecular components are basically
given by chemical reactions or associations between
chemical components:


X  Y 
 X Y


X  Y 
 X :Y
Covalent bonds
Association of molecules
Chemical Transformation Properties
• Stoichiometry – the stoichiometry of chemical
reactions is fixed and is described by integral
numbers counting molecules that react and
that form
• Relative rates – all reactions inside a cell are
governed by thermodynamics.
• Absolute rates – the absolute rates of
chemical reactions inside cells are highly
manipulable.
Functional States
• The functional states of biological reactions
networks are constrained by the
physicochemical nature of the intracellular
environment.
• There is a highly developed spatiotemporal
organization that orients the biological
components and determines the transient
nature of the interactions.
Theory-Based vs Constrain Based
Analysis
Source: Palsoson, B. 2006. System Biology
Constraining Allowable Functional
States
• A network can fundamentally have many
different states or many different solutions.
• Network have many different dehaviors that
are picked based on evolutionary history.
• Networks can carry out the same function in
many different and equivalent ways.
Hierarchical organization
Microbial Communities?
Source: Palsoson, B. 2006. System Biology